Impact of glycolysis inhibitor (2-DG) and oxidation and phosphorylation uncoupler (2,4-DNP) on brain metabolites

Deviations in brain metabolism are the result of longterm pathological processes, which finally are manifested as symptoms of Parkinson’s or Alzheimer’s diseases or multiple sclerosis and other neuropathologies, as for example diabetic neuropathy. A deficiency of available energy for brain cells under neurodegenerative diseases is either developed due to age-dependent underexpression of genes that encode glycolytic enzymes or induced due to the uncoupling of oxidation and phosphorylation that could be mediated by inflammatory cytokines. Since the activity of many enzymes is under the control of adenosine triphosphate (ATP) or cofactors, such as nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), energy deficiency can cause metabolic changes in brain tissue. Some clinical studies using proton nuclear magnetic resonance spectroscopy (1H NMR spectroscopy) revealed metabolic changes in brain tissue in patients with neurodegenerative diseases. However, data from different authors are quite contradictory, probably because of the complex genesis of metabolic disorders. In the present study, we tested the hypothesis of multidirectional changes in metabolism under the impact of the oxidation and phosphorylation uncoupler 2,4-dinitrophenol (2,4-DNP) and under the impact of 2-deoxy-Dglucose (2-DG), blocking the access of glucose to the brain cells. 1H NMR spectroscopy showed that 2-DG leads to the predominance of excitatory (glutamine + glutamate) neurotransmitters over inhibitory ones (gamma-aminobutyric acid), and 2,4 DNP causes opposite effects. The biochemical mechanisms of the observed changes require a special study, but it can be noted that the ATP deficiency caused by inhibition of glycolysis and the ATP deficiency caused by the uncouplers are accompanied by differently directed changes in the intensity of the tricarboxylic acid cycle. These changes in the intensity of the Krebs cycle are correlated with differently directed changes in the balance of the exciting and inhibitory neurotransmitters. The obtained results show that 1H NMR spectroscopy can be an effective method of differentiated lifetime assessment of the available energy deficit caused by a general suppression of energy exchange in nerve cells or oxidation and phosphorylation uncoupling

Brain metabolites in ISIAH and Wistar rats

Hypertension is one of the most common human diseases. This disease leads to serious disturbances such as myocardial infarction and stroke. Due to the development of nuclear magnetic resonance spectroscopy (NMRS), a decrease in neuron viability in different parts of the brain in humans with hypertension has been shown. Translation of NMRS tools to the clinic requires the accumulation of empirical data about neurometabolic changes in a strictly controlled experiment. It is particularly interesting to compare the metabolic parameters of laboratory animals with normal and high blood pressure kept in standard conditions on exactly the same diet. In this study, cortex and hypothalamus metabolites of ISIAH and Wistar male rats at the age of 8–9 weeks were examined. Cortex and hypothalamus metabolites were measured in animals under isoflurane anesthesia using proton magnetic resonance spectroscopy (1Н MRS). Processing of primary data using Partial least squares Discriminant Analysis (PLS-DA) allowed us to identify the main discriminating axis (Y1), its variations reflecting the predominance of excitatory neurometabolites (glutamine and glutamate) over inhibitory ones (GABA and glycine). In the cortex, the values of the Y1-axis were lower in ISIAH than in Wistar rats. This fact indicates a decrease in cortical excitability in hypertensive animals. By contrast, in the hypothalamus, the values of the Y1-axis were higher in ISIAH than in Wistar rats and the predominance of excitatory neurometabolites positively correlated with the level of mean blood pressure, which agrees well with the view of caudal hypothalamic activation in hypertensive animal models

Radioluminescence properties of nanocomposite scintillators with BaF 2 fillers

In this paper, studies of the luminescence properties of nanocrystalline BaF 2 samples synthesized by laser ablation and pulse electron beam evaporation method are presented. The measurements of X-ray excited luminescence (XEL) showed the dependence between luminescence intensity and the shape of the spectrum on the morphology and particle size. Also, studies of X-ray excited luminescence, decay curves and optical transmittance for nanocomposite materials containing BaF 2 nanopowder are presented. Barium fluoride nanopowder, obtained by pulsed electron beam evaporation method is characterized by a lower intensity than the initial microcrystalline powder, but at the same time, XEL spectrum of the nanocomposite material with this nanocrystalline filler is more intense, then that for nanocomposite material with initial powder. © Published under licence by IOP Publishing Ltd

The effect of a single administration of streptozotocin on hippocampus metabolites in NODSCID mice

The significant increase in the number of people diagnosed with diabetes mellitus in recent years makes studies of this problem topical. The persistent hyperglycemia accompanying the development and course of type 1 diabetes mellitus (T1DM) can affect the func-tional and structural levels of the organization of the central nervous system. These changes may be medi­ated by metabolic aberrations. Magnetic resonance spectroscopy (MRS) is a common method of intravital detection of metabolic reactions. In this study, MRS of the hippocampus of NOD.CB17-Prkdcscid/NcrCrl mice (NODSCID) was performed 4 days after the administration of streptozotocin (STZ) to assess the effect of STZ itself, and 60 days after the administration of STZ to another group of animals to assess the effect of chronic hyperglycemia caused by the delayed ef­fect of STZ, involving the death of pancreatic β-cells. The simulation of T1DM by STZ administration is used worldwide. Nevertheless, the question remains whether there is a short-term effect of the introduc­tion of STZ at the level of hippocampal metabolites recorded by MRS. The comparison of experimental and control animal groups revealed no effect of STZ on metabolites in the hippocampus of NODSCID mice on day 4 after its administration. In contrast, another comparison of the experimental and control animals on day 60 after STZ administration showed elevated contents of alanine and taurine, and a reduced lactate content. Thus, the introduction of STZ itself does not affect the metabolism of the hippocampus, and MRS is a promising method for assessing the effect of T1DM on brain metabolism in animals

Prevention of traumatic brain injury complications in sports

The aim of the review is to inform doctors and trainers of sports teams about technologies that prevent complications of sport brain injuries (SBI). Low levels of visibility of clinical manifestations, specific characteristics of individual reactions to injury, anti-aggravation behavior among sportsmen, absence of unbiased methods of diagnostics of SBI are the main reasons behind underestimation of the severity of trauma. Treatment and rehabilitation procedures of mild SBI do not currently consider specific characteristics of trauma, associated with the increase in body and brain temperature and reduced cerebral perfusion during the traumatizing intervention. Injury of the brain causes an increase in cerebral temperature, which, in turn, can aggravate the consequences of traumatization. The control of the temperature of the brain can be achieved with non-invasive method of microwave radiometry, while the technology of craniocerebral hypothermia (CCH), which has evident neuroprotective properties, can aid in the prevention of complications of SBI

Study of the neuronal response to olfactory stimuli in control and LPS-stimulated mice by functional magnetic resonance imaging

Olfactory perception plays the key role in the inter­action of animals with biotic factors of the species-specific econiche. Identification of odorants informs nocturnal animals about social environment, presence of predators, or infected food. Olfactory efficiency depends on physiological conditions; in particular, odor sensitivity can be changed by infection. This work considers use of fMRI in the study of the influence of innate immunity activation on neuronal response during perception and differentiation of socially significant (2.5-dimethylpyrazine, 2-heptanon) and socially insignificant (1-hexanol and isoprene) olfactory stimuli by CD-1 mice. We stimulated innate immunity by intraperitoneal injection of bacterial lipopolysaccharide (LPS) at the dose 500 µg/kg three hours before tomography. Urethane anesthesia was used during MRI trail. Odor stimulation was done with a lab-made metering unit for supplying standard doses of volatile organic compounds. The supply of olfactory stimuli induced activation of neurons in the primary perceptual center and the centers of secondary processing of olfactory information. Olfactory stimulus type affected neuronal response rate in an olfactory bulb but did not affect response parameters in other brain regions studied. This increase in neuronal activity is likely to be of adaptive significance as a mechanism supporting olfactory sensitivity increase, which plays the key role in the identification of potential sources of infection

NMR metabolic profiling of the liver following administrationof alcohol andthemushroom Ganoderma lucidum in rats

We have evaluated the efficiency of a metabonomic approach to metabolic phenotyping and detection of early metabolic changes under a toxic influence. For this purpose, a metabolic profiling of rat liver was performed with 1H NMR spectroscopy. Rat tissues from animals in three groups were analyzed. Group C consisted of control animals; animals in group A received alcohol repeatedly (15 % ethanol); and animals in group A+ R received alcohol in combination with a hepatoprotective herbal medicine (Reishi, Ganoderma lucidum) repeatedly. Noteworthy, alcohol consumption did not cause pathological changes, but stimulated hepatocyte proliferation. Our data suggest that changes in metabolite concentrations in A represent a typical metabolic response to alcohol consumption, namely decrease in glycine, leucine, isoleucine, valine, choline and lactate content, and increase in TMAO content. Treatment with Reishi (A+ R) had positive effects, in that it restored the levels of glycine, valine and TMAO. Furthermore, increase in NAD, ATP, UTP, succinate, pyranose, and acetate concentrations was observed in A+ R. A correlation was found between the valine, isoleucine, lactate, cho­line, and pyranose content and the num­ber of binuclear hepatocytes. Binuclear hepatocytes indicate proliferative activity, and the concentration of the metabolites participating in the formation of new hepatic cells decreases. Thus, the study of liver tissues by 1H NMR spectroscopy allows for detection of early changes in metabolite concentra­tions following chronic consumption of alcohol at insignificant doses. Consequently, 1H NMR spectro­scopy can serve as a promising approach to detecting alcohol-related liver pathologies and assessing the efficiency of the therapy used

Magnetic resonance spectroscopy of hippocampal and striatal neurometabolites in experimental PTSD rat modeling

The spectrum of the metabolites in the dorsal region of the hippocampus and striatum was studied using the method of 1H magnetic resonance spectroscopy at experimental modeling of the posttraumatic stress disorder syndrome (PTSD) in rats. PTSD was reproduced by exposure of the cat cue to rats daily along 10 day by 10 minutes at once. The anxiety level of animals was estimated 12 days later after the end of the experimental series of stress. Based on the anxiety index, the rats were divided into 3 phenotypes. The animals with an anxiety index > 0.8 (group 1) had lower plasma corticosterone compared with rats form the control group. In animals with an anxiety index in the range 0.7–0.8 (group 2), an elevated corticosterone level was noted. The rats with an anxiety index < 0.7 (group 3) had a lower plasma corticosterone level compared with animals from the control group. Rats of group 2 were characterized by an increased level of GABA in the hippocampus compared with controls. In the remaining groups, the percentages of GABA in the hippocampus and striatum did not differ significantly from the control. The distribution of NAA differed form that of GABA. The highest level of NAA was found in the striatum for rats from group 1, whereas NAA in animals form groups 1 or 3 did not differ from the control. The NAA level in the hippocampus was similar between all groups, including the control. The results obtained indicate that multiple exposures to psychological stress associated with the sense of proximity of a natural enemy in some animals cause an anxiolytic reaction. These animals are characterized by a stable corticosterone level and a stable level of neurometabolites in the studied structures of the brain. For rats with the highest level of anxiety, a lowered level of corticosterone with a constant level of neurometabolites in the hippocampus and striatum is characteristic. And only in rats with an intermediate level of anxiety, synchronization was observed between the increase in plasma corticosterone and the increase in hippocampal GABA content. The results obtained are in good agreement with the ideas of the protective action of glucocorticoids under PTSD manifested in  restraining violations of the psycho-physiological status. The mate rials allow the neurobiological mechanisms of the protective action of glucocorticoids to be detailed

Anxiety and neurometabolite levels in the hippocampus and amygdala after prolonged exposure to predator-scent stress

Here, to study the relationship between anxiety levels with changes in the neurometabolic profile in the hippocampus and amygdala, an experimental predator stress model was reproduced in which Sprague-Dawley rats were exposed to cat urine for 10 minutes on a daily basis for 10 days. At the time of presentation of the stimulus, an online survey of behavioral reactions was conducted. Fear, aggressiveness, avoidance of stimulus and grooming were recorded. Fourteen days after the completion of the last stress exposure, the total level of anxiety was determined in the test of the“cross maze”. Using the method of in vivo NMR spectroscopy, the content of neurometabolites was determined in the hippocampus and in the amygdala. According to the peculiarities of behavioral reactions to a stressor, animals were retrospectively divided into two phenotypes. The first phenotype used a passive behavioral strategy, and the second phenotype was active. In animals of the first phenotype, the indicators of anxiety behavior remained at the control level. In animals of the second phenotype, a decrease in anxiety was observed. Animals of the second phenotype showed elevated levels of lactate in the hippocampus compared to animals of the first phenotype, and the lowest N-acetylaspartate levels significantly differed from those in the control and the first phenotype animals. In the amygdala, in animals of the second phenotype, the content of taurine is sharply reduced in comparison with those in the control and the animals of the first phenotype. Thus, the results obtained indicate a relationship of post-stress changes in anxiety, with the peculiarities of the behavioral reactions presented at the moment of the immediate action of the stressor. Among the hippocampal and amygdala neurometabolites, the most informative for the characterization of the anxiolytic action of the predator stress are identified